Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
MDS, CMML, allogeneic stem cell transplantation, 5-azacytidine
Brief summary
5-azacytidine treatment prolongs survival in patients with myelodysplastic syndrome (MDS), but does not cure the disease. Allogeneic stem cell transplantation is a curative treatment option but is associated with a high risk treatment-related morbidity and mortality. In the current trial allogeneic stem cell transplantation will be compared to 5-azacytidine only treatment according to donor availability in elderly patients with MDS (55-70 years).
Detailed description
5-azacytidine treatment prolongs survival in patients with myelodysplastic syndrome (MDS), but does not cure the disease. Allogeneic stem cell transplantation is a curative treatment option but is associated with a high risk treatment-related morbidity and mortality. Dose-reduced conditioning prior transplantation allows also treatment of elderly patients with MDS. In the current trial allogeneic stem cell transplantation will be compared to 5-azacytidine only treatment according to donor availability in elderly patients with MDS (55-70 years).
Interventions
PROCEDUREallogeneic stem cell transplantation
donor available, after 4 cycles 5-azacytidine allogeneic stem cell transplantation after reduced conditioning
PROCEDURE5-azacytidine until progress
if no donor available 5-azacytidine until progress or toxicities
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with proven de novo or therapy-related MDS / CMML (WBC \<13 GPT/l)according to FAB and risk profile according to IPSS: intermediate II- risk or high-risk or intermediate I with high-risk cytogenetic (according to IPSS, taking into account that IPSS, however, was not validated for t- MDS), patients with secondary AML (according to WHO) and blasts ≤ 30 % (= RAEB-t according to FAB) * Previously untreated or maximal 1 cycle of 5-azacytidine (Vidaza®) * Male or Female; Age 55 - 70 years * Understand and voluntarily sign an informed consent form * ECOG performance status of ≤ 2 at study entry * Adequate renal and liver function: creatinine and bilirubin \< 3 x the upper limit of normal * Sufficient cardiac function (ejection fraction \> 30 %)
Exclusion criteria
* Blasts \> 30 % in bone marrow at time of diagnosis * Central nervous involvement * Severe irreversible renal, hepatic, pulmonary or cardiac disease, such as * Total bilirubin, SGPT or SGOT ≥ 3 times upper the normal level * Left ventricular ejection fraction \< 30 % * Creatinine clearance \< 30 ml/min * DLCO \< 35 % and/or receiving supplementary continuous oxygen * Pregnant or breastfeeding female subject * Patients with a life-expectancy of less than six months because of another debilitating disease * Serious psychiatric or psychological disorders * Uncontrolled invasive fungal infection at time of registration * Known positive for HIV or acute infectious hepatitis, type A, B or C * Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment until the end of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | three years | compare to overall survival of patients who receive after 4 cycles of 5-azacytidine either allogeneic stem cell transplantation or continuous 5-azacytidine if no compatible donor is available overall 230 patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| event-free survival | three years | comparison of event free survival in both arms (230 pat.): \- evaluation of survival status (relapse, date of relapse, alive or death) in the whole study period |
| overall survival | three years | Comparison of overall survival between both arms (230 pat.). \- evaluation of survival status (alive or death/date of death) in the whole study period |
| impact of Comorbidity-index on outcome | three years | impact of comorbidity-index on outcome after study entry and prior to allogeneic stem cell transplantation (according definitions and weighted scores of comorbidities by Sorror et al): * physical examination * laboratory values(creatinine,Alt, AST, bilirubin, etc.) * apparative diagnostics (echo,lufu,ECG) |
| response | three years | Comparison of response according to International Working Group Response Criteria between both arms: \- Examinations of bone marrow (count of blasts) and peripheral blood (hematological improvement)after schedule of study assessments (after cycle 4 in both arms, after cycle 8 and after months 12-24-36 in the 5-azacytidine treatment and on day 100, day 180, months 12-24-36 after allogeneic stem cell transplantation |
| Evaluation of toxicity | three years | the evaluation of toxicity will be performed according to the reporting guidelines as per NCI CTCAE in the whole study period: * adverse events grade 3 and 4 * cytopenia grade 3 and 4 only be reported as AE which are judged by the investigator as clinically relevant |
| quality of life | three years | Comparison of quality of life between both arms with the quality of life core questionnaire QLQ-C30 and the treatment specific high-dose chemotherapy module QLQ HD-C29 to assess the quality of life of cancer patient. The questionnaire has to be answered after the fourth cycle, 6 months, 1 year, 2 years and 3 years after both treatment arms |
| Treatment-related mortality | three years | compare treatment related mortality in both arms (230 pat.): \- death according to treatment in both arms |
Countries
Germany
Outcome results
None listed